Publications

the nature of the scrapie agent.	there now seems little doubt that the infective agent of scrapie cannot be accommodated within current concepts of virology/molecular biology. it is proposed: that the basic infective entity is a nucleic acid fragment (oligonucleotide) of some 40 bp coupled with specific (but host encoded) protein totalling approximately 10(5) daltons, a significant proportion of which is in the form of proteolipid; that the nucleic acid fragment reprograms the host cell on the chemically switched microprocessor ...	1986	3088402
separation and properties of cellular and scrapie prion proteins.	purified preparations of scrapie prions contain a sialoglycoprotein of mr 27,000-30,000, designated prp 27-30, which is derived from the scrapie prion protein [mr, 33,000-35,000 (prp 33-35sc)] by limited proteolysis. under these same conditions of proteolysis, a cellular protein of the same size (prp 33-35c) is completely degraded. subcellular fractionation of hamster brain showed that both prp 33-35sc and prp 33-35c were found only in membrane fractions. nacl, edta, and osmotic shock failed to ...	1986	3085093
monoclonal antibodies to the cellular and scrapie prion proteins.		1986	3090160
learning ability of mice infected with different strains of scrapie.	cd-1 mice were infected intraperitoneally with one of 4 different strains of scrapie and tested simultaneously at or near the end of incubation. there were no differences between any of the scrapie injected groups and controls in spontaneous motor activity, or in the shock thresholds and entry latencies measured during training in a one-trial passive avoidance test. on testing, the avoidance responses were normal for the mice infected with 22c or me7, but these mice did not show overt clinical s ...	1986	3088623
scrapie, ribosomal proteins and biological information.	consideration of the autocatalytic synthesis of ribosomal proteins leads to a criterion for the infectivity of a foreign proteinaceous species in terms of the biochemical rate constants governing the propagation of errors during the translation of genetic information in a model system. evidence pertaining to the suggestion that scrapie and its analogues are caused by proteinaceous infectious agents (prions) which replicate by invading the translation process and altering ribosomal specificity is ...	1986	3099090
from prions to prionic viruses.	the pathogens causing scrapie and other similar degenerative neurological diseases are called "prions" and classified either as viruses or, more often, as a novel class of pathogens. it is argued herein that prions are not the pathogens producing these diseases. the pathogens involved are endogenous viral systems inherited by the host. these endogenous parasites, tentatively named prionic viruses, produce the prions which are horizontally transmitted. the prions trigger the pathological manifest ...	1986	3090406
[the structure of the infectious scrapie agent].		1986	3104895
quicker progress on slow diseases.		1986	2908806
alterations of the functional properties of the parallel fibers in the cerebellum of the "scrapie mouse".	alterations of the functional properties of the cerebellar parallel fibers have been investigated in scrapie mice by recording the compound action potential elicited by the superficial stimulation of the cerebellum. as soon as the 12th week following intracerebral inoculation, i.e. during the silent incubation period, there is a clear decrease of the response amplitude and of the recruiting properties. depth profiles of the response indicate the progressive disappearance of the most superficial ...	1986	3017249
scrapie and its association with 'amyloid-like' fibrils and glycoproteins encoded by cellular genes: an animal model for human dementia.		1986	3107063
human prion protein cdna: molecular cloning, chromosomal mapping, and biological implications.	a human complementary dna whose protein product is considered to be the major component of scrapie-associated fibrils in creutzfeldt-jakob disease, kuru, and gerstmann-straussler syndrome has been identified and characterized. the extensive homology of this gene sequence to the hamster prp 27- to 30-kilodalton prion protein complementary dna clone, and its existence as a single copy in the human genome, leads to the conclusion that this is the human prion gene. this human prion gene has been map ...	1986	3014653
aids virus and scrapie agent share protein.		1986	3018589
linkage of prion protein and scrapie incubation time genes.	a single gene (prn-i) that affects scrapie incubation period in mice has been identified. i/lnj mice have a very long incubation period after inoculation of scrapie prions (200-385 days) and nzw/lacj mice have a short one (113 +/- 2.8 days). (nzw x i/ln)f1 hybrid mice had incubation times of 223 +/- 2.8 days indicating longer incubation times were dominant. incubation periods in the backcross progeny of (nzw/lacj x i/lnj)f1 x nzw/lacj segregated into two groups (64 mice, 130 +/- 1.1 d; 66 mice, ...	1986	3015416
scrapie prion proteins are synthesized in neurons.	scrapie is a slow degenerative encephalopathy of animals caused by unusual infectious particles termed prions. a cdna encoding the only apparent component of the prion, a protein designated prp 27-30, has recently been cloned and sequenced. by measuring mrna levels using in situ hybridization with the prp cdna, the authors found that prion proteins are synthesized almost exclusively within neurons. the levels of prp mrna varied among different types of neurons, but did not change during scrapie ...	1986	3079955
pathogenesis of scrapie (strain 263k) in hamsters infected intracerebrally, intraperitoneally or intraocularly.	after intracerebral (i.c.) infection of hamsters, the 263k strain of scrapie replicated at a nearly constant exponential rate until clinical disease developed when titres in brain averaged 9.8 log10 ld50 i.c. units/g. after intraperitoneal infection, scrapie replication was first detected in spleen, then in thoracic spinal cord and finally in lumbar cord and brain. this pattern suggests that invasion of the central nervous system occurs by spread of infection along certain visceral autonomic ner ...	1986	3080549
molecular hybridization studies with scrapie brain nucleic acids. i. search for specific dna sequences.	chromatography and hybridization techniques employing scrapie enriched fractions of hamster brains were employed to detect a scrapie-specific dna molecule. 125i-labeled dna from eight different scrapie-enriched hamster brain fractions was hybridized to total dna and rna from normal and scrapie hamster and mouse and to dna from normal human brain and brain tissue from patients dying with creutzfeldt-jakob disease. enrichment for infectivity was obtained by cellular partition, gel filtration and g ...	1986	3082311
immunoreactivity of a synthetic pentadecapeptide corresponding to the n-terminal region of the scrapie prion protein.	a pentadecapeptide with an amino acid sequence corresponding to the amino-terminal region of the scrapie prion protein was synthesized. immunization of a rabbit with the peptide conjugated with ovalbumin induced specific antibodies. the antibodies reacted with all three of the major polypeptides in a proteinase k-treated fraction obtained from brains of mice infected with the obihiro strain of scrapie agent. some peptides in the proteinase-untreated fraction also shared antigenicity with the thr ...	1986	3090197
[creutzfeldt-jakob disease in france. value of familial forms. is there a gene controlling the length of the incubation period?].	an extensive search for patients who died of creutzfeld-jakob disease in france between 1968 and 1982 resulted in the discovery of 327 cases, 233 of which were histologically proven and 29 transmitted to animals; 17 patients belonged to 6 families. further investigations among members of these 6 families yielded 21 additional cases, i.e. a total of 38 familial cases. studies among sibships suggested an autosomal dominant pattern of transmission but did not exclude lateral contamination infancy. ...	1986	2938156
transmissible mink encephalopathy (tme) in chinese hamsters: identification of two strains of tme and comparisons with scrapie.	tme from a single source was transmitted by intracerebral injection to chinese hamsters, producing clinical disease in all seven animals after incubation periods of over 600 days. the brain from each of the primary cases was used to establish separate intracerebral passage-lines of tme and this led to the isolation of two different strains of agent, designated 333k and 333w. these strains were easily distinguished by the incubation periods they produced (about 130 and 230 days, respectively) und ...	1986	2940469
evidence that transmissible mink encephalopathy agent is biologically inactive in mice.	transmissible mink encephalopathy (tme) is probably a form of the sheep disease, scrapie, introduced by accidentally feeding mink with scrapie-infected sheep tissues. although no successful transmissions of tme to mice have been achieved previous work has involved various limitations. to maximize the possibility of transmission, 176 mice, representing 14 different genotypes mostly not previously tested with tme, were injected with tme-infected mink brain from three sources with different histori ...	1986	2940470
cerebrocortical degeneration in goats inoculated with mink-passaged scrapie virus.	widespread spongiform degeneration of the cerebral cortex occurred in four african pygmy goats that became affected with scrapie after intracerebral inoculation with scrapie virus (suffolk sheep brain origin) that had been passed three times in ranch mink. the occurrence of such cerebrocortical degeneration was a distinct departure from the topographic pattern of neuropathologic changes that characterizes scrapie in sheep and goats. but the cortical lesion was identical to the one found in goats ...	1986	2946103
pathogenesis of scrapie: study of the temporal development of clinical symptoms, of infectivity titres and scrapie-associated fibrils in brains of hamsters infected intraperitoneally.	after an intraperitoneal infection of hamsters with scrapie agent, early low and constant titres of about 100 ld50/brain between days 10 to 50 were followed by a dramatic increase to maximum levels of 3 x 10(9) ld50/brain within about 15 days. the plateau of maximum infectivity remained unchanged from day 70 to the time of the first and final signs of disease at 95 and 123 days post-infection, respectively. scrapie-associated fibrils (saf) as measured by immunoblotting of saf protein could not b ...	1986	2875123
localization of a human gene homologous to the prp gene on the p arm of chromosome 20 and detection of prp-related antigens in normal human brain.	infectious fractions prepared from scrapie-infected hamster brains contain a protein, prp 27-30, which shares antigenic determinants with polypeptides found in similarly prepared fractions from patients with creutzfeldt-jakob disease. cdna sequences encoding the hamster prp 27-30 identified homologous sequences in the human genome as well as in normal human brain mrna preparations. antibodies raised against the mouse prp's identified antigenically related peptides in both normal hamster and huma ...	1986	2877664
scrapie: how much do we really understand?	biological studies have produced convincing evidence for different scrapie strains, some of which undergo mutation. this argues strongly in favour of the infectious scrapie agent having a genome. the length of incubation period is influenced by the strain of agent but is also under strict host control. in mice, this control is exerted by a gene called sinc which affects the overall rate of agent replication in the cns. after peripheral infection, invasion of the cns from lymphoreticular sites of ...	1986	2872607
scrapie and cellular prp isoforms are encoded by the same chromosomal gene.	prp 27-30 is the major protein in purified preparations of scrapie agent. an almost complete prp cdna was used to select prp-related genomic clones from normal hamster dna. the gene contains a noncoding exon of 56 to 82 bp and a 2 kb coding exon, separated by a 10 kb intron. transcription initiates at the same multiple sites in vivo and in vitro. the promoter lacks a tata box and contains three repeats of the sequence gccccgccc, which resembles the sp1 binding site found in "housekeeping" genes. ...	1986	2873895
scrapie-associated fibrils (saf) purification method yields amyloid proteins from systemic and cerebral amyloidosis.	we identified fibrils from non-transmissible systemic and cerebral amyloidosis using the purification method of scrapie-associated fibrils (saf). the fibrils possessed the same nature of congophilia, filamentous structures and molecular weights as amyloid fibrils, and were resistant to proteinase k digestion. this saf method makes for a rapid extraction from amyloid-laden tissues. the method, therefore, may purify nontransmissible amyloids alone or together with saf proteins.	1986	2874846
membrane filtration of scrapie agent.		1986	2868224
conservation of the cellular gene encoding the scrapie prion protein.	the major protein, prp 27-30, in purified preparations of hamster scrapie prions is encoded within the genome of the experimental host. dna sequences related to a prp cdna clone can be detected in a wide variety of organisms under relatively stringent conditions where the only signal generated by hamster or mouse dna corresponds to the prp gene. three hosts for scrapie, goat, sheep and rat gave strong hybridization signals. in addition, three invertebrate dnas reacted with the prp probe, in the ...	1986	2870469
molecular characteristics of prion rods purified from scrapie-infected hamster brains.	purification of scrapie prions from hamster brains has demonstrated that the infectious particles contain one major protein, prp 27-30. this protein, which is required for and inseparable from scrapie infectivity, polymerizes into heterogeneous rod-shaped particles measuring 10-20 nm in diameter and 100-200 nm in length. we attempted to identify the minimal infectious unit by disrupting aggregates of the rods. prolonged sonication resulted in progressive fragmentation of the rods into spherical ...	1986	2872252
the major protein of saf is absent from spleen and thus not an essential part of the scrapie agent.	scrapie-associated fibrils (saf) play a controversial role in the discussion about the nature of the scrapie agent. in purification experiments saf can be detected in brains of infected animals but not in spleen samples with similar titers of infectivity. thus, saf are not a constituent of the scrapie virus.	1986	2877648
suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions.	studies of polyanions that suppress scrapie have been done to pinpoint the cell types in the lymphoreticular system which are important in pathogenesis and to suggest possible prophylactic or therapeutic strategies for the unconventional slow viruses. a regime of three daily injections of the inorganic heteropolyanion hpa-23 reduced the effective scrapie dose by more than 99%; i.e., some mice survived peripherally injected doses of 100 50% lethal dose units. the effect was greatest when the firs ...	1986	2430521
prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection.	a single intraperitoneal injection of 250 micrograms dextran sulphate 500 (ds500) reduced the susceptibility of mice to scrapie given by the same route. a lower dose (25 micrograms) was less effective but still produced significant incubation period lengthening, while a high dose (2.5 mg) further increased the degree of prolongation. this reduced susceptibility occurred with ds500 administered up to at least 4 weeks prior to intraperitoneal scrapie inoculation and up to at least 2 weeks after sc ...	1986	2419489
molecular hybridization studies with scrapie brain nucleic acids. ii. differential expression in scrapie hamster brain.	rna and dna fractions prepared from nucleic acids obtained from normal and scrapie-infected hamster brains following exhaustive treatment with nuclease were used as probes in a search for a specific scrapie nucleic acid. employing rna blot hybridization a 2.3 kb rna was detected in higher concentration in scrapie-infected hamster brains than in normal controls. our data suggests that scrapie disease may be associated with the differential expression of a series of host genes.	1986	2420312
the pathogenesis of slow virus infections: molecular analyses.	slow infections raise some novel issues in understanding the pathogenesis of viral diseases that have been increasingly addressed at the molecular level with in situ hybridization. these developments are reviewed as the framework for discussion of the realized and potential impact of these investigations for major neurological afflictions of humans and for aids.	1986	2419455
a 54-kda normal cellular protein may be the precursor of the scrapie agent protease-resistant protein.	scrapie is the best understood of the transmissible spongiform encephalopathies. these neurologic disorders include the human diseases kuru and creutzfeldt-jakob disease and are caused by pathogens with unique biological and molecular properties. one major protein, protease-resistant protein (prp)-27-30, is present in fractions isolated from scrapie-infected hamster brain that contain highly purified scrapie agent. prp-27-30 appears to be the major protein component of the hamster scrapie agent. ...	1986	2421288
changes in the serotonergic, noradrenergic and dopaminergic levels in the brain of scrapie-infected rats.	levels of serotonin (5-ht), 5-hydroxyindoleacetic acid (5-hiaa), dihydroxyphenylacetic acid (dopac) and 3,4-dihydroxyphenylethyleneglycol (dhpg) were determined by high-performance liquid chromatography in different brain areas of scrapie-infected rats, 8.5 months after intracerebral inoculation of a rat-adapted strain from mice brain (c 506). at this time, rats developed early clinical signs of the disease. scrapie-infected rats showed a reduction in the levels of 5-ht and 5-hiaa (frontal corte ...	1986	2421836
partial copurification of scrapie-associated fibrils and scrapie infectivity.	the association between scrapie infectivity and scrapie-associated fibrils (saf) during a partial purification procedure for infectivity was investigated. scrapie infectivity and saf can be separated from most membrane components by subcellular fractionation of infected mouse brain to obtain a synaptosomal fraction, followed by detergent treatment and density gradient centrifugation. after different detergent treatments, with either octyl glucoside or sodium n-lauroyl sarcosinate, saf showed dif ...	1986	2422138
immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains.	scrapie-associated fibrils (safs) are abnormal filamentous structures that are uniquely associated with unconventional slow virus diseases. the antigenic relationships of safs from animals infected with four biologically distinct scrapie strains were investigated by using antisera raised to purified saf proteins. rabbit antisera were raised to safs isolated from mice infected with the me7 scrapie strain and to safs isolated from hamsters infected with the 263k scrapie strain. a strong antigenic ...	1986	2426470
antibody to scrapie-associated fibril protein identifies a cellular antigen.	antibody to scrapie-associated fibril (saf) protein was produced in a rabbit by a primary injection of 50 brain equivalents of native saf protein emulsified in complete freund's adjuvant and by a secondary inoculation of polyacrylamide gel which contained 50 brain equivalents of saf protein emulsified with incomplete freund's adjuvant. the antibody produced was found to decorate the saf as demonstrated by the use of goat anti-rabbit colloidal gold second antibody. immunoblots (dot blots and west ...	1986	2418150
scrapie and cellular prion proteins share polypeptide epitopes.	purified preparations of scrapie prions contain one major protein, prp 27-30, and aggregates of rod-shaped structures. on the basis of the nh2-terminal amino acid sequence of prp 27-30, a synthetic peptide (prp-p1) was constructed. monospecific rabbit antisera to prp-p1 were found by immunoblotting to react with prp 27-30 and its precursor (prp 33-35sc), as well as with a related protease-sensitive cellular homologue (prp 33-35c). an enzyme-linked immunosorbent assay showed that rabbit antiserum ...	1986	2422294
detection of scrapie-associated fibril (saf) proteins using anti-saf antibody in non-purified tissue preparations.	antisera raised to scrapie-associated fibril (saf) proteins were used to detect scrapie-specific polypeptides in three different non-purified brain preparations: a synaptosomal-mitochondrial fraction, 20% brain homogenate and 20% brain homogenate extracted with sarkosyl. the concentration of saf proteins in the preparations was greater than the quantity of saf as detected by negative stain electron microscopy. this suggests that not all of the protein exists in the form of saf. an immunologicall ...	1986	2420924
amyloid plaques in creutzfeldt-jakob disease stain with prion protein antibodies.	amyloid plaques are found in the brains of some patients with creutzfeldt-jakob disease (cjd) and all patients with a related transmissible disorder, gerstmann-sträussler syndrome (gss). in scrapie, a prion disease of animals, amyloid plaques have been shown to be composed of prion proteins (prp), which form filaments of relatively uniform diameter. we report here that antisera raised against hamster scrapie prp specifically stain amyloid plaques in the brains of both humans and rodents with cjd ...	1986	3092727
characterization of major peptides in creutzfeldt-jakob disease and scrapie.	in creutzfeldt-jakob disease three major peptides cosediment with the infectious agent. these distinct peptides are not present in identical fractions from uninfected brain, and bind to polyclonal antibodies raised against "prion protein" purified by protease treatment. three similar distinct peptides are also found in scrapie-infected brain fractions purified without the use of proteases. to clarify the relationships between these distinct peptides and prion protein, peptides were analyzed on i ...	1986	3090551
recent developments in scrapie and creutzfeldt-jakob disease.		1986	3092282
assignment of the human and mouse prion protein genes to homologous chromosomes.	purified preparations of scrapie prions contain one major macromolecule, designated prion protein (prp). genes encoding prp are found in normal animals and humans but not within the infectious particles. the prp gene was assigned to human chromosome 20 and the corresponding mouse chromosome 2 using somatic cell hybrids. in situ hybridization studies mapped the human prp gene to band 20p12----pter. our results should lead to studies of genetic loci syntenic with the prp gene, which may play a rol ...	1986	3094007
replication of scrapie prions in hamster eyes precedes retinal degeneration.	progressive degeneration of outer retinal structures occurs in hamsters with scrapie. in order to determine the relationship between histopathologic changes and replication of the scrapie agent, hamsters were inoculated intracerebrally with approximately 10(7) id50 units. animals sacrificed at 50 days after inoculation showed no signs of neurologic dysfunction, but had high titers of the scrapie agent or prions in both neural and nonneural portions of the eye. prion titers in retina were greater ...	1986	3095759
the major polypeptide of scrapie-associated fibrils (saf) has the same size, charge distribution and n-terminal protein sequence as predicted for the normal brain protein (prp).	scrapie-associated fibrils (saf) are unique structures characteristic of the group of unconventional slow infections which includes scrapie and creutzfeldt-jakob disease. a major component of hamster fibrils has been described as a protease-resistant glycoprotein with an apparent mol. wt of 27,000-30,000 (prp27-30). however, we report here that if fibrils are prepared by procedures designed to minimise proteolysis the prp proteins co-purifying with hamster saf have mol. wts of 33,000-35,000 (prp ...	1986	3096712
scrapie incubation periods and end-point titers in mouse strains differing at the h-2d locus.	in extending findings on the influence of the mouse h-2d locus on the scrapie incubation period, we showed that with the intracerebral (i.c.) route of injection, sjl and nzw mice (s and z alleles, respectively) had shorter incubation periods than c57bl mice (b allele) at several concentrations of two scrapie strains, me7 and 139a. the three mouse strains have the same sinc genotype, s7s7. incubation period data among the three mouse strains after intraperitoneal (i.p.) injection revealed a diffe ...	1986	3106258
biology and structure of scrapie prions.		1986	3100471
diagnosis of creutzfeldt-jakob disease by western blot identification of marker protein in human brain tissue.	we tested purified preparations of brain tissue from 39 patients with creutzfeldt-jakob disease, gerstmann-sträussler-scheinker syndrome, or kuru, and from 32 patients with a variety of nonspongiform degenerative diseases, with the use of western blots against an antiserum to a similarly purified fraction made from scrapie-infected hamster brain. positive reactions occurred in 81 percent of the 31 specimens from the patients with creutzfeldt-jakob disease (and in all of the 7 specimens that were ...	1986	3511385
[prions--a new microbiological and neurological problem].		1986	3520517
isolation of a cdna clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues.	we have isolated a hamster cdna clone representing the coding sequences for the entire precursor of prion protein (prp) 27-30. this clone encodes a protein of 254 residues and contains an in-frame atg codon 42 bases upstream from the one previously reported. analysis of the predicted amino acid sequence suggests that the prp precursor protein contains an amino-terminal signal sequence, and a membrane-spanning domain in the carboxyl terminus. cleavage of the signal peptide would produce a mature ...	1986	3529083
transmissible virus dementia: evaluation of a zoonotic hypothesis.	creutzfeldt-jakob disease (cjd) and kuru are subacute transmissible dementing encephalopathies characterized by spongiform changes in the brain. scrapie is a similar slow viral encephalopathy which affects sheep, goats and certain other animals. anecdotal reports suggest that creutzfeldt-jakob disease could be a zoonosis. to evaluate the possibility that cjd is acquired from animals, a case-control study was conducted on 26 well-documented cjd cases and 40 controls. data were collected on exposu ...	1986	3550507
[virion or prion? second thoughts on the physicochemical structure of the infective agent in scrapie].		1986	3550513
prions are novel infectious pathogens causing scrapie and creutzfeldt-jakob disease.		1986	3551942
neuronal cytoskeleton in aging and dementia.		1986	3554352
spread of scrapie agent to the central nervous system: study of a rat model.	invasion of scrapie agent into the central nervous system (cns) was studied in rats following intracerebral and peripheral inoculation, the latter by injection into intact or transected sciatic nerve. comparison of sleep-wakefulness alterations, neuropathological features, and time lag of electroencephalographic and clinical signs in the 3 groups suggests that hematogenous spread of infection to the cns may predominate over neural transport, and that peripheral inoculation may closely approximat ...	1986	3094830
brain histamine metabolism in transmissible spongiform encephalopathy (scrapie).	the histamine (hi) content and the activity of l-histidine decarboxylase (hd) in brains of scrapie infected hamsters were measured. no significant changes in hi levels in particular brain areas were found when compared to controls. decreased activity of hd was found in hypothalamus (p less than 0.02). increased activity of the enzyme was observed in "rest of brain", which consisted mainly of thalamus and striatum (p less than 0.05).	1986	3711883
cerebrovascular amyloidosis in scrapie-affected sheep.	cerebrovascular amyloidosis (ca) was found in the cerebral and cerebellar cortices in 11 of 20 sheep, of six different breeds, with naturally-occurring scrapie. the occurrence of the lesion did not appear to be influenced by the age of the sheep. this was not seen in 20 brains from age- and breed-matched sheep with other conditions. furthermore, it was not found in 20 sheep experimentally infected with scrapie by sub-cutaneous inoculation, or in 22 sheep with natural scrapie in a closed breeding ...	1986	3713984
retinopathy in mice with experimental scrapie.	scrapie is a naturally occurring neurological disease of adult sheep and goats with an incubation period of several years. some strains of the causal agent can infect laboratory mice in which the incubation period, as well as the severity and distribution of vacuolar degeneration in the brain, varies according to the strain of the agent and the genotype of the mouse. retinopathy, involving the partial or complete loss of the photoreceptor layer, was observed in a number of murine scrapie models ...	1986	3713985
degenerative neurites in experimental scrapie.		1986	3748406
spongiform encephalopathy in sheep scrapie: electron microscopic observations.		1986	3761785
[light and electron microscopic observations of sheep scrapie].	two suffolk sheep diagnosed as scrapie clinically and epidemiologically were investigated light and electron microscopically. they were female and four years four months of age. spongiform lesions were found in the gray and white matter of midbrain, pons, medulla oblongata, spinal cord and the cerebellar white matter as well as the cerebral gray and white matter. ultrastructurally, the spongiform lesions were shown to be caused by vacuolation in neuronal perikarya, vacuolation and/or swelling of ...	1986	3768187
study of endemic scrapie in a flock of "ile de france" sheep.	an "ile de france" flock was studied over a period of 5 years. the authors found similar results concerning incidence and age of onset of scrapie to those found in the english literature. a close relationship was established between the age of the dam at parturition and the age of the progeny at onset of scrapie. in the later years of our study, scrapie was detected in younger animals than in the earlier years, suggesting a phenomenon of genetic "anticipation". increased fecundity in this endemi ...	1986	3770148
gliocytosis in experimental scrapie (263k strain of scrapie) in golden syrian hamsters.		1986	3785689
chromatin structure in scrapie and alzheimer's disease.	scrapie affected brains exhibit a number of pathological features in common with the human neurodegenerative condition, alzheimer's disease. the present report describes studies on chromatin structure seen in these two disease processes. chromatin associated proteins influence transcriptional activity of dna through an effect upon chromatin structure. we examined chromatin structure by: measuring the capacity of the enzyme micrococcal nuclease to release mono- and dinucleosomes from isolated nuc ...	1986	3791058
primary retinopathy in scrapie in mice deprived of light.	rodents infected with some strains of scrapie develop a severe retinopathy in which the photoreceptor cells are destroyed. the possibility that this results from light-induced damage as a secondary consequence of the disease was tested by maintaining scrapie-infected albino mice in total darkness. photoreceptor loss occurred in terminal scrapie-infected mice maintained in both total darkness and in normal lighting conditions establishing that the retinopathy is a primary lesion with this strain ...	1986	3808457
molecular cloning and complete sequence of prion protein cdna from mouse brain infected with the scrapie agent.	the prion protein (prp) is a scrapie-associated fibril protein that accumulates in the brains of hamsters and mice infected with the scrapie agent, and also in the brains of persons affected with kuru or creutzfeldt-jakob disease. it has been previously proposed that prp could be either the primary transmissible agent of scrapie or a secondary component involved in the pathogenesis of scrapie. at present, the second possibility seems more likely, for the prp-specific mrna is present in both infe ...	1986	3462700
[transmissible spongiform encephalopathy. natural diseases and experimental studies].		1986	3295591
effect of bacterial flora and mouse genotype (euthymic or athymic) on scrapie pathogenesis.	euthymic and athymic female balb/c mice, reared under either germfree or defined flora conditions, were used to investigate the pathogenesis of scrapie after intracerebral or intraperitoneal inoculation. time in days to onset of clinical signs (stage i), to endstage (stage ii), and the time interval between stage i and stage ii were compared among groups. in addition, scrapie agent titers in spleen were determined at 28 and 90 days after infection, as were agent titers in spleen and brain at sta ...	1986	3464673
electroencephalogram and evoked potentials in naturally occurring scrapie in sheep.	electroencephalogram (eeg), brain stem auditory-evoked potential, and flash visual-evoked potential recordings were taken from healthy sheep and from 3 sheep with scrapie, a cns slow virus infection. the eeg changes included semi-periodic, polyphasic, high-voltage sharp waves (bilaterally synchronous and symmetric in all channels), and a cyclic alternating pattern consisting of a high-voltage low-frequency phase, followed by a low-voltage high-frequency phase. the high-voltage phase occurred wit ...	1986	3963585
familial creutzfeldt-jakob disease in france: epidemiological implications.	of 329 patients dying of creutzfeldt-jakob disease (cjd) in continental france between 1968 and 1982, 19 (6%) were familial cases. genealogical investigation permitted the identification of 19 additional cases, bringing the total number of familial cjd cases reported here to 38. there are 6 definitely affected families, yielding an average of 6.3 cases per family. mediterranean jews account for one-third of all the cases, with tunisian jews constituting two-thirds of this ethnic group. males and ...	1986	3542553
pituitary growth hormone and creutzfeldt-jakob disease.		1986	3296633
molecular cloning of a human prion protein cdna.	creutzfeldt-jakob disease (cjd) of humans and scrapie of animals are degenerative, transmissible neurologic diseases caused by prions. the only known macromolecules within prions are prion proteins (prp). the cdna encoding the hamster prion protein (prp 27-30) has been cloned and sequenced (oesch et al., 1985). using that hamster prp cdna, we screened a human retina cdna library and sequenced the cdna clone with the longest hybridizing insert. this insert was found to contain a long open reading ...	1986	3755672
[autocatalytic nature of "slow virus infections"].	a concept that considers the causative nature of the so-called "slow virus infections", causing syndromes of spongiform encephalopathies in man and animals as a chain autocatalytic process is put forward. according to this concept, prp(27-30) protein, isolated recently from the brains of scrapie-infected animals, is a c-terminal domain of the normal protein component of brain tissue which is a latent zimogen. certain clinical and experimental data are discussed within the framework of this conce ...	1986	3543657
brain tumours in mice, with particular reference to astrocytoma.	in a survey of 75,000 brains from 23 inbred mouse strains studied during research work on scrapie, astrocytoma was by far the commonest neuroectodermal tumour. it occurred in vm and brvr mice at a 1% incidence, but was virtually absent from other strains. in vm mice it occurred nearly twice as often in males as in females, sometimes causing neurological signs of circling, depression or spinal paralysis, but more often showing no clinical effects and being discovered only during routine neuropath ...	1986	3957158
lectin histochemistry of scrapie amyloid plaques.	peroxidase-labeled lectins were used for detection of specific monosaccharide residues in amyloid plaques in brains of scrapie-infected mice. the lectins tested recognize the following residues: beta-d-galactosyl (ricinus communis agglutinin 120, rca-1), alpha-d-galactosyl and alpha-d-galactopyranoside (bandeirea simplicifolia aggl., bsa), alpha-d-mannosyl and alpha-d-glucosyl (concanavalin a, con a), n-acetylglucosaminyl and sialyl (wheat germ aggl., wga), sialoglycoconjugates (limulus polyphem ...	1986	3962600
injury-related spinal cord astrocytes are immunoglobulin-positive (igm and/or igg) at different time periods in the regenerative process.	igg-positive astrocytes have been reported in scrapie-induced and alzheimer's cortical plaques, multiple sclerosis, and cns tissue around abscesses, metastatic tumors and primary tumors of glial origin. the present experiments ascertain if this immunoglobulin positivity is specific for these cases or a function of astrocytes around any site of injury in the cns. the spinal cords of 30, 300-g sprague-dawley male rats were lesioned by passing a 26 gauge needle through the cord at t6. after periods ...	1987	3690308
abnormal tubulovesicular particles in brains of hamsters with scrapie.	abnormal tubulovesicular particles of an average diameter of 23 nm have been observed in brains of mice with scrapie as well as in other animals with spongiform encephalopathies, but they were thought to be absent from the brains of hamsters with scrapie in which the highest known concentrations of the infectious agent occur. we observed in neuronal processes of hamsters as well as mice clusters of those tubulovesicular structures, most often in postsynaptic terminals. such particles have now be ...	1987	3562457
incubation periods and survival times for mice injected stereotaxically with three scrapie strains in different brain regions.	incubation period and survival time were determined in c57bl mice which had been injected stereotaxically with either the 139a, me7 or 22l strain of scrapie in one of five different brain regions (cerebral cortex, caudate nucleus, thalamus, substantia nigra, cerebellum). the injection of 139a in the caudate nucleus, thalamus, substantia nigra or cerebellum resulted in significantly shorter incubation periods than following cerebral cortex injection. for me7, mice injected in the thalamus and cer ...	1987	3546594
an electron and light microscopic study of the numbers of dystrophic neurites and vacuoles in the hippocampus of mice infected intracerebrally with scrapie.	numbers of dystrophic neurites, seen with the electron microscope, in ca1 of the hippocampus of either c3h mice infected with 22c or 79a strains of scrapie, or lm mice infected with strain me7 were greater than in age-matched control mice. vacuolation, seen by light microscopy in ca1 of the hippocampus of mice infected with either 22c or 79a, preceded the increase in dystrophic neurites by up to about 20 days. in mice infected with me7, however, the vacuolation followed the increase in dystrophi ...	1987	3618130
on the biology of prions.	prions cause scrapie and creutzfeldt-jakob disease (cjd); these infectious pathogens are composed largely, if not entirely, of protein molecules. no prion-specific polynucleotide has been identified. purified preparations of scrapie prions contain high titers (greater than or equal to 10(9.5) id50/ml), one protein (prp 27-30) and amyloid rods (10-20 nm in diameter x 100-200 nm in length). considerable evidence indicates that prp 27-30 is required for and inseparable from scrapie infectivity. prp ...	1987	3554880
prions causing degenerative neurological diseases.	prions cause degenerative neurological diseases--scrapie in animals and creutzfeldt-jakob disease in humans. the novel properties and structure of the prion distinguish it from viruses.	1987	3555303
scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: a quantitative golgi analysis.	an altered morphology of neuronal dendrites has been shown to be associated with many degenerative diseases of the central nervous system (cns). scrapie is a cns degenerative disorder caused by a novel infectious particle or prion. golgi impregnation studies showed that neurons in the scrapie-infected brains of hamsters contained varicose swellings and diminished numbers of dendritic spines. in order to ascertain whether or not these differences were statistically significant, quantitative metho ...	1987	3598605
ultrastructural observations of spinal cord lesions and blood-brain barrier changes in scrapie-infected mice.	spinal cord samples from im or vm mice injected intracerebrally with the 87v scrapie agent were examined ultrastructurally at the clinical stage of disease for changes in blood vessel permeability and for pathological alterations. in several animals, (3 of 16), massive changes were noted in the cervical spinal cords in the subependymal area of the cortical gray matter immediately surrounding the central canal including ependymal cell changes, the presence of amyloid plaque in close association w ...	1987	3604572
neuronal origin of cerebral amyloidogenic proteins: their role in alzheimer's disease and unconventional virus diseases of the nervous system.	the protein component of alzheimer's disease amyloid (neurofibrillary tangles, amyloid plaque cores and congophilic angiopathy) is an aggregated polypeptide with a subunit mass of approximately 4 kda (the a4 monomer). the aggregational properties of this monomer may explain the amyloidogenic nature of the protein: the native monomer forms dimers, tetramers and higher oligomeric species which are dependent on ph, ionic strength and concentration; the synthetic peptide corresponding to residues 1- ...	1987	3556089
immunoblotting of creutzfeldt-jakob disease prion proteins: host species-specific epitopes.	creutzfeldt-jakob disease (cjd) is a rare dementia that is generally found in older people and is caused by unusual infectious pathogens or prions. using rabbit antisera raised against hamster scrapie prion proteins (haprpsc), we identified by immunoblotting human cjd prion proteins (huprpcjd) in the brains of 14 patients dying of cjd. extracts from 6 of the patients were transmitted to mice after prolonged incubation. the rabbit antisera raised against haprpsc also reacted with the mouse cjd pr ...	1987	3300520
pathogenesis of scrapie is faster when infection is intraspinal instead of intracerebral.	previous studies of mice infected peripherally with 139a scrapie showed that scrapie agent initially replicates outside the cns and that invasion of the cns occurs several weeks later by neural spread of infection along visceral autonomic fibres to the mid-thoracic cord, and thence to brain. direct intracerebral infection of brain bypasses the need for extraneural replication and gives shorter incubation periods than peripheral routes. however, it was also found that the duration of the scrapie ...	1987	3148813
cerebellar lamellar bodies in two strains of murine scrapie.	lamellar inclusion bodies have been described by other authors in the granular layer of the cerebellum of people suffering from the unconventional slow-virus disease of kuru and were thought to be associated with the disease. in this study, these bodies were also found in mice infected with scrapie, which belongs to the same group of diseases, as well as their age-matched controls.	1987	3668000
evidence for a secretory form of the cellular prion protein.	the biogenesis of hamster brain prion protein (prp) has been studied by expression of rna transcribed from a full-length prp cdna in xenopus oocytes and cell-free systems. earlier studies in the wheat germ cell-free system showed that one form of prp is a transmembrane protein that spans the bilayer at least twice [hay, b., barry, r. a., lieberburg, i., prusiner, s. b., & lingappa, v. r. (1987) mol. cell. biol. 7, 914-920]. we now report that prp can also exist as a secreted protein. sp6 prp rna ...	1987	3126796
the molecular pathogenesis of astrogliosis in scrapie and alzheimer's disease.	in slow infections caused by scrapie and other unconventional agents, and in alzheimer's disease (ad), the formation of neuritic plaques and the increase in astrocytes and astrocyte-specific protein, glial fibrillary acidic protein (gfap), are pathological changes common to both conditions. with the rationale that these parallels imply convergent pathogenetic mechanisms, we identified a gene whose expression increases in both. we now report the results of a more extensive analysis of this gene a ...	1987	3507557
[creutzfeldt-jakob disease: report of a case].	a case of creutzfeldt-jakob disease (cjd) in a 76 year-old man is presented. the clinical picture included a rapid progressive dementia associated with ataxia, global aphasia, myoclonus and pyramidal signs; death occurred after about 4 months. there was an antecedent of chemical trauma caused by plant liquid on right eye 12 to 18 months before. the electroencephalogram showed diffuse slow activity and the neuropathological findings were typical. the detection of a protein called "prion" or prp27 ...	1987	3300614
[slow viruses].		1987	3321384
the epidemiology of creutzfeldt-jakob disease: conclusion of a 15-year investigation in france and review of the world literature.	during the 15-year period 1968-1982, a total of 329 patients dying of creutzfeldt-jakob disease (cjd) were identified in continental france. annual mortality rates stabilized at 0.5 to 0.6 cases per million (1.1 to 1.2 cases per million in paris). six percent of cases were familial. although the frequency of cjd was related to population density, no contacts could be established among the great majority of patients. no association with socioeconomic factors, preceding trauma or surgery (exceptin ...	1987	3295589
ovine abomasal enlargement and scrapie.		1987	3576941
detection of scrapie-associated fibrils as an aid to the diagnosis of natural sheep scrapie.		1987	3590556
scrapie-induced obesity in mice.		1987	3598239
developmental expression and regional distribution of the scrapie-associated protein mrna in the rat central nervous system.	the scrapie associated protein (sap) has been shown to be a normal brain protein of yet undefined function. this study demonstrates that rat brain sap mrna levels undergo a transcriptionally dependent increase during normal development. the interregional variation in the adult rat central nervous system (cns) is roughly 10 fold, with highest levels in the basal ganglion/thalamus and lowest levels in the spinal cord.	1987	2443218
biogenesis and transmembrane orientation of the cellular isoform of the scrapie prion protein [published errratum appears in mol cell biol 1987 may;7(5):2035].	considerable evidence suggests that the scrapie prion protein (prp) is a component of the infectious particle. we studied the biogenesis and transmembrane orientation of an integral-membrane form of prp in a cell-free transcription-linked translation-coupled translocation system programmed with a full-length prp cdna cloned behind the sp6 promoter. translation of sp6 transcripts of the cdna or of native mrna from either normal or infected hamster brain in the absence of dog pancreas membranes re ...	1987	3547085
scrapie associated fibrils in the diagnosis of scrapie in sheep.	previous research has consistently demonstrated by electron microscopy the presence of scrapie associated fibrils in brain extracts prepared from mice and hamsters with clinical signs of experimental scrapie. in the present study similar fibrils were seen in all the brain extracts prepared from 11 cheviot or suffolk sheep with natural or experimental scrapie that had been diagnosed clinically and confirmed neuropathologically. they were not found in the brain extracts of nine sheep that did not ...	1987	3604027